The present invention relates to compounds containing the .alpha. phenylethyl group finding particular, but not necessarily exclusive, utility in the synthesis of peptides, and more specifically in the solid phase synthesis of peptides. More particularly, the present invention relates to the use of phenylethyl compounds as applied to polymer carriers for the synthesis of peptides and peptide amides, particularly in connection with the solid phase synthesis thereof.
Peptide synthesis has been greatly facilitated by the development of solid phase peptide synthesis (SPPS) in which peptide chains are assembled on an insoluble polymer bead as a carrier. An automated mechanism for the solid phase synthesis of peptides is disclosed in U.S. Pat. No. 3,531,258, issued Sept. 29, 1970, to R. B. Merrifield, J. M. Stewart and N. Jernberg for "APPARATUS FOR THE AUTOMATED SYNTHESIS OF PEPTIDES". In the solid phase peptide synthesis, the bond which holds the first amino acid to the polymer carrier is an extremely important one. Currently available bonds for the synthesis of simple peptides involve a benzyl ester linkage, while those for the synthesis for peptide amides, which are utilized in connection with many hormones, involves a benzhydryl amide linkage. One of the principal problems is that the bonds formed on currently available carrier resins are so stable that the conditions needed to sever the peptide from the carrier are so drastic that damage occurs to the peptide.
The solid phase synthesis of peptides is extensively described by John M. Stewart and Janis D. Young in "Solid Phase Peptide Synthesis" published by W. H. Freeman & Company, San Francisco 1969. Stewart and Young describe the chemistry of solid phase peptide synthesis, laboratory techniques and apparatus, and the book includes extensive appendixes on apparatus, chemicals and reagents, amino acids, protecting groups and reagents, and a bibliography of references. Stewart and Young describe in detail the chemical aspects of the resin support and many protecting groups. Where necessary for a more complete understanding of the present invention, reference should be made to the Stewart and Young book, and such book is by reference incorporated herein.